Jain Ashok, Kashyap Randeep, Demetris Anthony J, Eghstesad Bijan, Pokharna Renu, Fung John J
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Liver Transpl. 2002 Jan;8(1):40-6. doi: 10.1053/jlts.2002.29763.
Hepatitis C is the most common indication for liver transplantation (LT) in the United States. Recurrence of hepatitis C virus (HCV) infection post-LT remains a problem for which there is no completely satisfactory treatment. The aim of the present study is to evaluate mycophenolate mofetil (MMF), which has both immunosuppressive and antiviral properties, to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival. Between August 1995 and May 1998, a total of 106 patients who were HCV positive before LT were randomized to tacrolimus (TAC) and prednisone versus TAC, prednisone, and MMF therapy. The rate of recurrence of HCV, patient and graft survival, incidences of rejection, and histological findings were examined. Fifty six patients were randomized to TAC and steroid therapy (double [D] drug; group D), and 50 patients were randomized to TAC, steroid, and MMF therapy (triple [T] drug; group T). Liver biopsies were performed when liver function was abnormal; protocol liver biopsies were not performed. Mean follow-up was 4.3 +/- 0.8 years. Actuarial patient survivals at 4 years were 72.6% in group D and 73.8% in group T (P = not significant). Actuarial graft survivals at 4 years were 65.6% in group D and 65.4% in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV. One patient in each group died of recurrent HCV without re-LT. Twenty-six patients in group D (46.4%) and 23 patients in group T (46.0%) showed signs of recurrent HCV. Mean hepatitis activity index (HAI) scores were 7.4 +/- 2.7 in group D and 7.0 +/- 3.4 in group T, and mean fibrosis scores were 2.9 +/- 1.7 in group D and 2.6 +/- 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period. None of these values reached statistical significance. Rates of HCV recurrence, graft loss or death from recurrent HCV, and 4-year actuarial patient and graft survival were not different between the groups. In liver transplant recipients with HCV, MMF has no impact on patient survival, graft survival, rejection, or rate of HCV recurrence based on biochemical changes and histological findings. In addition, there was no difference in HAI or fibrosis score between the two groups. Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its antiviral effect in the clinical setting.
丙型肝炎是美国肝移植（LT）最常见的适应证。肝移植后丙型肝炎病毒（HCV）感染复发仍是一个问题，目前尚无完全令人满意的治疗方法。本研究的目的是评估具有免疫抑制和抗病毒特性的霉酚酸酯（MMF），以确定其是否与HCV复发率的差异有关，并研究其对患者和移植物存活的影响。1995年8月至1998年5月，共有106例肝移植前HCV阳性的患者被随机分为接受他克莫司（TAC）和泼尼松治疗组与接受TAC、泼尼松和MMF治疗组。检测HCV复发率、患者和移植物存活率、排斥反应发生率及组织学表现。56例患者被随机分配至TAC和类固醇治疗组（双药组；D组），50例患者被随机分配至TAC、类固醇和MMF治疗组（三药组；T组）。当肝功能异常时进行肝活检；未进行常规肝活检。平均随访时间为4.3±0.8年。D组4年实际患者生存率为72.6%，T组为73.8%（P无统计学意义）。D组4年实际移植物生存率为65.6%，T组为65.4%。D组1例患者和T组2例患者因HCV复发接受了二次肝移植。每组各有1例患者死于HCV复发且未再次进行肝移植。D组26例患者（46.4%）和T组23例患者（46.0%）出现HCV复发迹象。D组平均肝炎活动指数（HAI）评分为7.4±2.7，T组为7.0±3.4，D组平均纤维化评分为2.9±1.7，T组为2.6±1.1。在整个随访期间，每组患者的排斥反应发生率均为0.57/患者。这些数值均未达到统计学意义。两组之间HCV复发率、因HCV复发导致的移植物丢失或死亡以及4年实际患者和移植物存活率均无差异。对于HCV阳性的肝移植受者，基于生化变化和组织学表现，MMF对患者存活、移植物存活、排斥反应或HCV复发率均无影响。此外，两组之间HAI或纤维化评分也无差异。在临床环境中，要么MMF没有抗HCV作用，要么其免疫抑制特性掩盖了其抗病毒作用。
